Molecular variants of HPV‐16 associated with cervical cancer in Indian population

Abstract

Human papilloma virus is a causative factor in the etiology of cervical cancer with HPV16 being the most prevalent genotype associated with it. Intratype variations in oncogenic E6/E7 and capsid L1 proteins of HPV 16 besides being of phylogenetic importance, are associated with risk of viral persistence and progression. The objective of this multicentric study was to identify HPV-16 E6, E7 and L1 variants prevalent in India and their possible biological effects. Squamous cell cervical cancer biopsies were collected from 6 centres in India and examined for the presence of HPV 16. Variants of HPV-16 were characterized by full length sequence analysis of L1, E6 and E7 genes in 412 samples. Similar distribution of the variants was seen from the different centres/regions, with the European variant E350G being the most prevalent (58%), followed by American Asian variant (11.4%). Fifty six changes were seen in E6 region, 31 being nonsynonymous. The most frequent being L83V (72.3%), Q14H (13.1%) and H78Y (12.1%). Twenty-nine alterations were seen in E7 region, with 12 being nonsynonymous. The most frequent being F57V (9%). L1 region showed 204 changes, of which 67 were nonsynonymous. The most frequent being 448insS (100%), and 465delD (100%), H228D (94%), T292A (85%). The identified variants some new and some already reported can disrupt pentamer formation, transcriptional regulation of the virus, L1 protein interface interaction, B and T cell epitopes, p53 degradation, and thus their distribution is important for development of HPV diagnostics, vaccine, and for therapeutic purpose. ' UICCKey words: cervical cancer; human papilloma virus 16; variants Cervical cancer is the second most predominant cancer worldwide. 1 In India it is the most common cancer amongst women, accounting for 130,000 new cases and more than 70,000 deaths annually. Persistent infection with high risk Human papilloma virus (HPV) is the main aetiological factor in the development of cervical cancer and may depend on HPV genotypes and variants. 2 HPV-16 is the most prevalent genotype associated with cervical carcinomas globally, as well as in Indian women. [3][4][5] This could perhaps be because of differential HPV-16 variant frequency, with certain variants conferring greater oncogenecity. 6,7 The molecular variants or lineages differ in nucleotide sequence by no more than 2% in the coding region and 5% in the noncoding regions of the viral genome with respect to the prototype. 8 Through nucleotide sequence comparisons, it has been found that HPV-16 has evolved along 5 major phylogenetic branches i.e., European, Asian, Asian American, African-1 and African-2. 9 Intratypic variation of HPV-16 has been shown to be an important predictor of progression to clinical relevant cervical lesion. 10 In a cohort study of young women 16 different HPV variants were found, one of which persisted over time, although the other variants were transiently detected. 11 Considerable intratypic diversity of HPV-16 has been reported by other studies based on DNA sequenc...

Genetic Diversity of HPV-16E6,E7, andL1Genes in Women With Cervical Lesions in Liaoning Province, China

“…The E7 variant A647G leading to a change from Asn to Ser at amino acid position 29 has been reported by Ding et al 18 However, this change should alter the functions of E7 protein including cell immortalization, activation of cyclins E and A, inhibition of cyclin dependent kinase inhibitors, enhancement of foreign DNA integration and mutagenecity. 19 Unlike that has been reported to be absent in India by Pande et al, 20 this variant was identified in 42.9% (61/142) of our samples. In a Korean study, 21 the E-prototype was detected in only 10% of patients of invasive cervical carcinomas, whereas the variant N29S was present in 70% of invasive cervical carcinomas.…”

Human Papillomavirus 16 Variants May Be Identified by <b><i>E6 </i></b>Gene Analysis

“…Previous studies have shown that some nucleotide substitutions have remarkable importance in pathogenicity [11,20,21,22]. In the present study, 16 nucleotide variations were detected.…”

Human papillomavirus genotyping by 454 next generation sequencing technology

“…Multiple-variant infections, which have been rarely described in the literature [16][17][18] , have epidemiological and diagnostic relevance. Some HPV intratype variants have been associated with geographic specificity and worldwide migration of the human host 19,20 , increased oncogenicity 21,22 , and might be responsible for escape to prophylactic vaccination 23 .…”